Human Molecular Genetics, Vol 7, 1437-1447, Copyright © 1998 by Oxford University Press
I Sahly, K Gogat, A Kobetz, D Marchant, M Menasche, M Castel, F Revah, J Dufier, M Guerre-Millo and MM Abitbol
The tubby strain of mice exhibits maturity-onset obesity and sensory
deficits in vision and hearing. The mutated gene, tub , responsible for
this phenotype was identified recently, but the function of the TUB protein
has not been deduced from its amino acid sequence. This prompted us to
undertake expression mapping studies with the hope that they might help to
elucidate the biological role of the TUB protein. We report the tub gene
expression pattern in embryonic, fetal and adult mice tissues as determined
by northern blots and in situ hybridization, using antisense
oligonucleotidic probes. In mouse embryos, tub is expressed selectively in
differentiating neurons of the ensemble of central and peripheral nervous
systems, starting at 9.5 days after conception. In adult mice, tub is
transcribed in several major brain areas, including cerebral cortex,
hippocampus, several nuclei of the hypothalamus controlling feeding
behavior, in the spiral ganglion of the inner ear and in the photoreceptor
cells of the retina. These structures contain potential cellular targets of
the tubby mutation- induced pathogenesis. The neuronal-specific tub gene
distribution allows the establishment of a genotype-phenotype correlation
in the tubby mice. This correlation is reminiscent of that observed in
fat/fat mice, whose phenotype, also characterized by obesity, is caused by
a null mutation in the carboxypeptidase E (CPE) gene. Our observations
highlight similarities between CPE, prohormone convertases, several
neuropeptides and tub gene expression patterns during embryogenesis, and
may narrow down the avenues to explore in order to determine ultimately the
function of the TUB protein.
ARTICLES
Prominent neuronal-specific tub gene expression in cellular targets of tubby mice mutation
CERTO, Faculte Necker, 156 rue de Vaugirard, 75015 Paris, France and INSERM U465, 15 rue de l'Ecole de Medecine, 75006 Paris, France.
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